Avoiding potentially negative outcomes is a common practice in human society. For instance, a person may drive to work earlier to avoid the negative consequences and stress associated with rush-hour traffic. In such circumstances, the traffic acts as a negative reinforcer, eliciting negative affect and strengthening the action of driving earlier. Negative reinforcers can have beneficial short-term influences on behavior by prompting one to actively cope with negative affect (e.g. avoiding traffic stress). However, an avoidance response can also become maladaptive if it prevents an individual from directly addressing the stressful event, causing long-term consequences such as fostering an addictive behavior (e.g., avoiding work deadlines and stress with drug use). These responses are difficult to extinguish and can become habitual, creating a burden for the individual and society. Thus, it is imperative to understand how aversive outcomes influence human brain and behavior. Non-human animal models of aversive learning highlight the role of striatal circuits, commonly implicated in reinforcement learning, in the acquisition of avoidance or coping responses (e.g., Salamone, 1994; LeDoux & Gorman, 2001). Yet, less is known about 1) human mechanisms of avoidance learning; 2) alternative means of coping with negative affect that are dependent on higher-order cognition and control and; 3) the influence of a pre-existing negative emotional state or stress on active coping strategies. The goal of this application is to investigate how negative reinforcement influences human brain and behavior as a precursor to understanding how humans learn to cope with potential negative outcomes that can influence decision-making in maladaptive ways (e.g., drug abuse to alleviate negative affect). The proposed studies will build on a solid and existing research foundation on affective learning in animals, which links the striatum and avoidance behavior, by first: establishing in humans the behavior and neural correlates of simple negative reinforcement tasks modeled after animal research; and second: examining alternative means of active coping with negative reinforcement that are more common to humans, such as higher-order cognitive strategies. Finally, proposed studies will examine the influence of a pre-existing acutely stressful state on active coping through avoidance or emotion regulation strategies. This approach allows for a translational method that can also be further extended to developmental (e.g., avoidance learning during adolescence) and clinical settings (e.g., mechanisms of active coping via emotion regulation during drug craving) in future research. PUBLIC HEALTH RELEVANCE: The proposed studies will build on a solid and existing research foundation on affective learning in animals by first: establishing in healthy human brains the behavior and neural correlates of simple negative reinforcement tasks modeled after animal research; and second: examining alternative means of active coping with negative reinforcement that are more common to humans, such as higher-order cognitive strategies. This approach allows for a translational method that can be applied to understanding the relationship between negative reinforcement and substance abuse, setting up future clinical investigations in substance-abusing populations (e.g., mechanisms of active coping via emotion regulation during drug craving).